Heteroatom Bond-forming Reactions Research Articles

ChemInform Abstract: Synthesis of Planar Chiral Ferrocenes by Transition‐Metal‐Catalyzed Enantioselective C—H Activation

AbstractReview: [27 refs.

Switching on elusive organometallic mechanisms with photoredox catalysis.

Transition metal-catalyzed cross-coupling reactions have become one of the most utilized carbon–carbon and carbon–heteroatom bond-forming reactions in chemical synthesis. More recently, nickel catalysis has been shown to participate in a wide variety of C–C bond forming reactions, most notably Negishi, Suzuki–Miyaura, Stille, Kumada, and Hiyama couplings1,2. Despite the tremendous advances in C–C fragment couplings, the ability to forge C–O bonds in a general fashion via nickel catalysis has been largely unsuccessful. The challenge for nickel-mediated alcohol couplings has been the mechanistic requirement for the critical C–O bond forming step (formally known as the reductive elimination step) to occur via a Ni(III) alkoxide intermediate. In this manuscript, we demonstrate that visible light-excited photoredox catalysts can modulate the preferred oxidation states of nickel alkoxides in an operative catalytic cycle, thereby providing transient access to Ni(III) species that readily participate in reductive elimination. Using this synergistic merger of photoredox and nickel catalysis, we have developed a highly efficient and general carbon–oxygen coupling reaction using abundant alcohols and aryl bromides. More significantly, we have developed a general strategy to “switch on” important yet elusive organometallic mechanisms via oxidation state modulations using only weak light and single-electron transfer (SET) catalysts.

ChemInform Abstract: Carbon—Hydrogen Bond Functionalizations Mediated by Copper

AbstractReview: [81 refs.

Use of In Situ Generated Nitrosocarbonyl Compounds in Catalytic Asymmetric α-Hydroxylation and α-Amination Reactions

Abstract Nitroso compounds are highly fascinating electrophiles as they are able to selectively transfer both the heteroatoms in a variety of oxidation reactions. Bench stable aryl-nitroso compounds are most extensively utilized for this purpose. However, the prominent success of aryl-nitroso chemistry is still immature because of the difficulty in the cleavage of N-aryl bond. Nitrosocarbonyl compounds with easily removable protecting groups (e.g. Boc and Cbz) on the other hand are more attractive reagents. They are highly reactive, easily manipulable, and readily available via the oxidation of N-protected hydroxylamines. However, the transient nature and incompatibility of the catalytic processes with their generation has incarcerated their use mostly in hetero-Diels–Alder and ene reactions. In this account we will summarize our efforts to utilize the nitrosocarbonyl compounds as a source of electrophilic oxygen and nitrogen in a variety of asymmetric carbon–heteroatom bond-forming reactions. The O- vs. N-selectivity can be tuned by switching reaction conditions. Thus, highly functionalized tertiary α-hydroxy and α-amino carboxylic acids, tertiary α-hydroxy phosphonic acid derivatives and β-amino alcohols were synthesized in high yields and high enantioselectivities using nitrosocarbonyl compounds as a source of electrophilic oxygen and nitrogen.

Carbon–Hydrogen Bond Functionalizations Mediated by Copper

Direct carbon–hydrogen bond functionalization has attracted considerable attention and plays a key role in organic transformations. Currently, copper is showing great potential as a catalyst in C–H bond-functionalization reactions because of its low cost and unique reactivity. This review summarizes the recent advances in copper-catalyzed C–H bond functionalizations from carbon–carbon and carbon–heteroatom (O, N and S) bond-forming reactions through activation of C–H bonds. 1 Introduction 2 Carbon–Carbon Bond Formation 2.1 Csp–H Bond Functionalization 2.2 Csp2–H Bond Functionalization 2.3 Csp3–H Bond Functionalization 3 Carbon–Heteroatom Bond Formation 3.1 Carbon–Oxygen Bond Formation 3.2 Carbon–Nitrogen Bond Formation 3.3 Carbon–Sulfur Bond Formation 4 Conclusion

Organometallic Nickel(III) Complexes Relevant to Cross-Coupling and Carbon–Heteroatom Bond Formation Reactions

Nickel complexes have been widely employed as catalysts in C-C and C-heteroatom bond formation reactions. In addition to Ni(0) and Ni(II) intermediates, several Ni-catalyzed reactions are proposed to also involve odd-electron Ni(I) and Ni(III) oxidation states. We report herein the isolation, structural and spectroscopic characterization, and organometallic reactivity of Ni(III) complexes containing aryl and alkyl ligands. These Ni(III) species undergo transmetalation and/or reductive elimination reactions to form new C-C or C-heteroatom bonds and are also competent catalysts for Kumada and Negishi cross-coupling reactions. Overall, these results provide strong evidence for the direct involvement of organometallic Ni(III) species in cross-coupling reactions and oxidatively induced C-heteroatom bond formation reactions.

ChemInform Abstract: Enantioselective C—C and C—Heteroatom Bond Forming Reactions Using Chiral Ferrocene Catalysts

AbstractReview: 252 refs.

ChemInform Abstract: Catalytic C—C and C—Heteroatom Bond Formation Reactions: In situ Generated or Preformed Catalysts? Complicated Mechanistic Picture Behind Well‐Known Experimental Procedures.

AbstractReview: 72 refs.

ChemInform Abstract: Recent Advances in the Use of Chiral Bronsted Acids as Cooperative Catalysts in Cascade and Multicomponent Reactions.

In recent years, chiral Bronsted acid catalysts have been widely used in numerous enantioselective carbon–carbon and carbon–heteroatom bond-forming reactions. Cascade/domino reactions and multicomponent reactions provide highly efficient, operationally simple, and atom-economical approaches to the synthesis of polyfunctional complex molecules that are useful for modern organic chemistry and drug discovery. The control of stereoselectivity in these reactions remains a great challenge. Chiral Bronsted acid catalysts were rationally introduced as bifunctional catalysts to achieve synergetic catalysis for well-controlled stereoselectivity. The synergy between chiral Bronsted acid catalysts and other compatible catalysts provides additional avenues for the discovery of novel organic transformations and improves reaction selectivity as well. In this Focus Review, recent advances in the uses of chiral Bronsted acids as cooperative catalysts in asymmetric cascade/multicomponent reactions are summarized.

Catalytic C–C and C–Heteroatom Bond Formation Reactions: In Situ Generated or Preformed Catalysts? Complicated Mechanistic Picture Behind Well-Known Experimental Procedures

In situ generated catalysts and preformed catalysts are two practical strategies widely used in cross-coupling methodology that have long been considered to involve the same active species in the catalytic cycle. Recent mechanistic studies have revealed two fundamentally different pictures of catalytic reactions in solution. Preformed catalysts with strongly bound ligands initiate transformations mainly involving single type of metal species. In contrast, in situ generated catalysts give rise to cocktail-type systems with different metal species presented in solution. The role of catalyst precursor, interconversions of catalytic species during reaction, stability and recycling of catalyst, catalysis by autocatalyst exhaust and plausible sources of metal-containing contaminants are the key points discussed in this review.

Very Small (3–6 Atoms) Gold Cluster Catalyzed Carbon–Carbon and Carbon–Heteroatom Bond‐Forming Reactions in Solution

Clusters get the gold: Atomic gold clusters Aun (n=3–6) are very active species (sub-mol %) for gold-catalyzed carbon–carbon and carbon–heteroatom bond-forming reactions of interest in organic synthesis. The gold clusters can be formed in situ or generated ex situ and introduced into the reaction media. Salts, complexes, and nanoparticles (NPs) can be used as a starting source of gold. Ts=para-toluenesulfonyl.

ChemInform Abstract: Mesitylcopper — A Powerful Tool in Synthetic Chemistry

AbstractReview: 197 refs.

Mesitylcopper – A Powerful Tool in Synthetic Chemistry

Since its first report in 1981, mesitylcopper has become an extremely popular and useful reagent, with many new applications emerging during the past decade. This review summarizes its structural and spectroscopic properties and gives a brief overview of the multitude of fascinating compounds and reactions that have been discovered by using mesitylcopper. Specifically, the role of mesitylcopper in synthesizing oligonuclear homo- and heteroleptic copper(I) frameworks, including biorelevant copper(I) complexes, and the application of mesitylcopper in stoichiometric and catalytic C–C and C–heteroatom bond-forming reactions and as a precursor for nanoparticles and intermetallic phases are covered.

ChemInform Abstract: Recent Advances in Transition‐Metal‐Free Carbon—Carbon and Carbon—Heteroatom Bond‐Forming Reactions Using Arynes

AbstractReview: ca. 100 refs.

Arynes in Transition‐Metal‐Free Multicomponent Coupling Reactions

Let's couple together! The multicomponent reactions involving arynes offer direct access to unusual heterocyclic scaffolds and 1,2-disubstituted arenes. This transition-metal-free, one-pot construction of molecular complexity is likely to play a pivotal role in various carbon–carbon and carbon–heteroatom bond-forming reactions.

Bimetallic Redox Synergy in Oxidative Palladium Catalysis

Polynuclear transition metal complexes, which are embedded in the active sites of many metalloenzymes, are responsible for effecting a diverse array of oxidation reactions in nature. The range of chemical transformations remains unparalleled in the laboratory. With few noteworthy exceptions, chemists have primarily focused on mononuclear transition metal complexes in developing homogeneous catalysis. Our group is interested in the development of carbon-heteroatom bond-forming reactions, with a particular focus on identifying reactions that can be applied to the synthesis of complex molecules. In this context, we have hypothesized that bimetallic redox chemistry, in which two metals participate synergistically, may lower the activation barriers to redox transformations relevant to catalysis. In this Account, we discuss redox chemistry of binuclear Pd complexes and examine the role of binuclear intermediates in Pd-catalyzed oxidation reactions. Stoichiometric organometallic studies of the oxidation of binuclear Pd(II) complexes to binuclear Pd(III) complexes and subsequent C-X reductive elimination from the resulting binuclear Pd(III) complexes have confirmed the viability of C-X bond-forming reactions mediated by binuclear Pd(III) complexes. Metal-metal bond formation, which proceeds concurrently with oxidation of binuclear Pd(II) complexes, can lower the activation barrier for oxidation. We also discuss experimental and theoretical work that suggests that C-X reductive elimination is also facilitated by redox cooperation of both metals during reductive elimination. The effect of ligand modification on the structure and reactivity of binuclear Pd(III) complexes will be presented in light of the impact that ligand structure can exert on the structure and reactivity of binuclear Pd(III) complexes. Historically, oxidation reactions similar to those discussed here have been proposed to proceed via mononuclear Pd(IV) intermediates, and the hypothesis of mononuclear Pd(II/IV) catalysis has guided the successful development of many reactions. Herein we discuss differences between monometallic Pd(IV) and bimetallic Pd(III) redox catalysis. We address whether appreciation of the relevance of bimetallic Pd(III) redox catalysis is of academic interest exclusively, serving to provide a more nuanced description of catalysis, or if the new insight regarding bimetallic Pd(III) chemistry can be a platform to enable future reaction development. To this end, we describe an example in which the hypothesis of bimetallic redox chemistry guided reaction development, leading to the discovery of reactivity distinct from monometallic catalysts.

Asymmetric Inverse‐Electron‐Demand Hetero‐Diels–Alder Reaction of Six‐membered Cyclic Ketones: An Enamine/Metal Lewis Acid Bifunctional Approach

The combination of organocatalysis with metal catalysis has emerged as a potentially powerful tool in organic synthesis. This new concept aims to achieve organic transformations that cannot be accessed by organocatalysis or metal catalysis alone. In our effort to combine organo-enamine catalysis with metal Lewis acid catalysis, we have developed a new class of bifunctional enamine/metal Lewis acid catalysts. These bifunctional catalysts displayed unusually high activity and high stereoselectivity in asymmetric direct aldol reactions. The challenge in the development of Lewis acid/Lewis base catalytic systems lies in the acid-base quenching reaction that leads to catalyst inactivation. A common and elegant approach to solving this problem is the use of a soft acid along with a hard base, or vice versa. Based on this approach, organo-enamine catalysis has been successfully combined with Cu, Ag, Pd, and Au. We use a different strategy to solve the acid-base problem. This new strategy complements the mixed soft/hard approach. In our system, the Lewis base (primary or secondary amine) is tethered to a chelating ligand, which serves as a “trap” for the incoming metal. In this way, the base and the metal Lewis acid are brought into close proximity in one molecule without interacting with each other (Figure 1). The bifunctional enamine/metal Lewis acid catalysts have two unique advantages. First, a large number of metals can be introduced. The Lewis acidity can be easily tuned by simply using a different metal, thereby offering great flexibility to this system. For example, stronger Lewis acids, such as La, can be used to activate the enamine acceptor more strongly. Second, the bifunctional catalysts can potentially convert an intermolecular reaction into a much more efficient intramolecular reaction. In addition, the intramolecular bifunctional nature of the catalysts would also enhance the stereoselectivity of the reaction. With these catalysts, we intend to develop new carbon–carbon or carbon–heteroatom bond-forming reactions involving difficult organic transformations. Herein, we report the first example of a highly chemoand enantioselective inverse-electron-demand hetero-Diels–Alder (HDA) reaction of cyclic ketones with b,g-unsaturated-a-ketoesters catalyzed by primary-amine-based enamine/metal Lewis acid bifunctional catalysts. Asymmetric inverse-electron-demand hetero-Diels– Alder (IED/HDA) reactions of electron-rich alkenes with an electron-deficient a,b-unsaturated ketone offers a valuable synthetic entry into dihydropyran derivatives, which are chemically and biologically of significant importance, allowing the construction of up to three stereogenic centers in one operation. In most of the inverse-electron-demand HDA reactions, enol ethers derived from aldehydes act as the electron-rich alkenes (dienophiles). Very recently, enaminebased organocatalytic asymmetric inverse-electron-demand HDA reactions, in which an in situ formed enamine from a chiral pyrolidine and an aldehyde serves as the dienophile, have been made possible. Ketones are much less reactive compared to aldehydes because of electronic and steric reasons. Asymmetric HDA reactions of ketones, in particular cyclic ketones, have remained a long-standing challenge. We are interested in developing a catalytic asymmetric enamine-based IED/HDA reaction of simple ketones with enones, as it would greatly generalize this method, and open it up to much wider exploitation. To achieve this we believe that the activation of enones should extend beyond hydrogen-bond methods, 8] for example, by using a strong metal Lewis acid. In contrast, the formation of a less congested enamine intermediate using a primary amine catalyst may also contribute to or facilitate this transformation. The primary-amine-based enamine/metal Lewis acid bifunctional catalysts developed in our laboratory appear to be ideal candidates to tackle this difficult problem. We envision that the primary amine/metal Lewis acid bifunctional catalyst would engage enone 3 and the cyclic ketone 2 intramolecularly (Scheme 1). The primary amine would form an enamine in situ with the ketone (A) and the Figure 1. Illustration of primary amine/metal Lewis acid bifunctional catalysts.

ChemInform Abstract: Copper‐Mediated Cross‐Coupling Reactions

AbstractReview: 493 refs.

Transition metal-catalyzed C–H activation reactions: diastereoselectivity and enantioselectivity

This critical review discusses historical and contemporary research in the field of transition metal-catalyzed carbon-hydrogen (C-H) bond activation through the lens of stereoselectivity. Research concerning both diastereoselectivity and enantioselectivity in C-H activation processes is examined, and the application of concepts in this area for the development of novel carbon-carbon and carbon-heteroatom bond-forming reactions is described. Throughout this review, an emphasis is placed on reactions that are (or may soon become) relevant in the realm of organic synthesis (221 references).

Relative Rates for the Amination of η3-Allyl and η3-Benzyl Complexes of Palladium

Reactions of nucleophiles with metal-bound hydrocarbyl pi-ligands bound in an eta3-fashion are key steps in a variety of carbon-carbon and carbon-heteroatom bond-forming reactions. To reveal factors that control the rates of reaction of nucleophiles with this type of ligand, the rates of reactions of an aromatic and an aliphatic amine with a series of eta3-allyl, eta3-benzyl, and eta3-phenethyl palladium complexes ligated by the bisphosphine (R)-BINAP to form allylic and benzylic amines were measured. These data showed that the less common addition to an eta3-benzyl complex is faster than the more common addition to an eta3-allyl complex. The relative rates of reaction followed the trend naphthylmethyl > naphthylethyl > benzyl > 1,1-dimethylallyl > allyl. Computational studies suggest that there is a correlation between the amount of positive charge at the site of nucleophilic attack and the rate of C-N bond formation.